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Critical Evaluation of the Changes in Glutamine Synthetase Activity in Models of Cerebral Stroke

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Abstract

The following article addresses some seemingly paradoxical observations concerning cerebral glutamine synthetase in ischemia–reperfusion injury. In the brain, this enzyme is predominantly found in astrocytes and catalyzes part of the glutamine-glutamate cycle. Glutamine synthetase is also thought to be especially sensitive to inactivation by the oxygen- and nitrogen-centered radicals generated during strokes. Despite this apparent sensitivity, glutamine synthetase specific activity is elevated in the affected tissues during reperfusion. Given the central role of the glutamine-glutamate cycle in the brain, we sought to resolve these conflicting observations with the view of providing an alternative perspective for therapeutic intervention in stroke.

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Notes

  1. Under normal intracellular physiological conditions (pH 7.2–7.4) ammonia exists predominantly (~99 %) as the conjugate acid, ammonium (NH4 +). Even so, the term ammonia is used throughout the text to indicate the sum of NH3 plus NH4 + for the sake of convenience.

  2. Görg et al. [39] refers to this residue as Tyr335.

Abbreviations

EPR:

Electron paramagnetic resonance

GABA:

γ-Aminobutyrate

MSO:

l-Methionine-S,R-sulfoximine

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Acknowledgments

Part of the work described in this review was supported by NIH grant DK 16739 (AJLC) and the Theresa Patnode Santmann Foundation (TMJ).

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY, 10595, USA

    Thomas M. Jeitner & Arthur J. L. Cooper

  2. Argonne National Laboratory, Argonne, IL, 60439, USA

    Kevin Battaile

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  1. Thomas M. Jeitner
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  2. Kevin Battaile
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Correspondence to Thomas M. Jeitner.

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Special Issue: In Honor of Dr. Gerald Dienel.

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Jeitner, T.M., Battaile, K. & Cooper, A.J.L. Critical Evaluation of the Changes in Glutamine Synthetase Activity in Models of Cerebral Stroke. Neurochem Res 40, 2544–2556 (2015). https://doi.org/10.1007/s11064-015-1667-1

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